Cederlöf Martin, Lichtenstein Paul, Larsson Henrik, Boman Marcus, Rück Christian, Landén Mikael, Mataix-Cols David
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden;
Schizophr Bull. 2015 Sep;41(5):1076-83. doi: 10.1093/schbul/sbu169. Epub 2014 Dec 15.
Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19,814), schizophrenia (n = 58,336), bipolar disorder (n = 48,180), and schizoaffective disorder (n = 14,904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice.
强迫症（OCD）常与精神病性障碍和双相情感障碍共病；这种共病使这些疾病的临床管理变得复杂。在这项基于人群的纵向多代家庭研究中，我们研究了这些疾病之间的共病模式、纵向风险和共同的家族风险。参与者包括1969年1月至2009年12月期间瑞典患者登记册中诊断为强迫症（n = 19,814）、精神分裂症（n = 58,336）、双相情感障碍（n = 48,180）和分裂情感性障碍（n = 14,904）的个体；他们的一级、二级和三级亲属；以及与人群匹配（1:10比例）的未受影响的对照个体及其亲属。瑞典处方药登记册用于在纵向分析中控制药物治疗的潜在影响。患有强迫症的个体患精神分裂症共病诊断的风险增加了12倍，患双相情感障碍和分裂情感性障碍的风险增加了13倍。纵向分析表明，首次诊断为强迫症的个体后来被诊断为所有其他疾病的风险增加，反之亦然。在调整了选择性5-羟色胺再摄取抑制剂的使用后，双相情感障碍的风险降低了，但并未消除。强迫症先证者未受影响的一级、二级和三级亲属患所有这三种疾病的风险显著增加；随着遗传距离的增加，这种风险的程度降低。我们得出结论，强迫症在病因上与精神分裂症谱系和双相情感障碍都有关。这些结果对当前的基因搜索工作和临床实践具有启示意义。
